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Updating data on  Clostridioides difficile  antibiotic resistance is important for treatment improvement of  C. difficile  infections (CDIs). Results from 20 countries were included. The mean resistance to 2 mg/l vancomycin, 2 mg/l metronidazole, 4 mg/l moxifloxacin, and 4 mg/l clindamycin was 4.7% (0 to ≥ 26% in two studies), 2.6% (0 to ≥ 40% in 3 studies), 34.9% (6.6-&gt;80%), and 61.0% (30-&gt;90%), respectively. Resistance to erythromycin (&gt;60–88%), rifampin (&gt;23–55.0%), imipenem (0.6 to &gt; 78% in a clone), tigecycline (0-&lt;5.0%), and fidaxomicin (0–2%) was also found. Resistance to ≥ 5 antibiotics of different classes was reported in some countries. High resistance and multidrug resistance were observed in hypervirulent and epidemic strains. Although only 1% of COVID-19 patients had CDIs, the proportion might be underestimated. C. difficile  antimicrobial susceptibility varied by country/region, study period, and circulating ribotypes. For CDI treatment, fidaxomicin (preferably) or vancomycin is recommended, while metronidazole is suitable for mild infections. New approaches, including biotherapeutics (Rebyota), strains, antibiotics (ridinilazole and ibezapolstat), and monoclonal antibodies/cocktails merit further evaluation. Because of the resistance rate variations,  C. difficile  antibiotic susceptibility should be regularly monitored. Post-COVID-19 resistance should be separately presented. Some discrepancies between vancomycin and metronidazole results need to be clarified.

Clostridioides difficile resistance to antibiotics, including post-COVID-19 data